Abstract The Bedford VA hospital requests for fund to acquire the Helios CyTOF time-of-flight atomic Mass Spectrometer (MS), manufactured by Fluidigm. Currently, our hospital MS laboratory is equipped with a Q Exactive hybrid Orbitrap MS, a Quantiva Triple Quadrupole MS, and a QSTAR MS/MS system. The new Helios CyTOF MS will combine cell cytometer, inductively coupled plasma, time-of-flight MS into a single instrument. It is completely different from existing MS instruments. With the addition of Helios CyTOF MS, we will expand core biomarker detection capability at the Bedford VA Hospital Research and Development program. This instrument will play an important role in multi-disciplinary clinical studies that are supported by VA, providing us with an unparalleled ability to phenotypically and functionally profile cells from normal and diseased states. The Helios CyTOF MS will be used for multiple VA funded studies directed by Drs. Xia, Stein and Hanlon (major users), along with other principal investigators (minor users) at the Bedford VA Hospital (Drs. Moo, Morin, Wells, Semenov), Boston VA Health System (Drs. Driver and Rasmusson), and Columbia VA Hospital (Dr. Gu). The Helios CyTOF MS will be used to analyze a large variety of biological samples for studies related to central nervous system disorders. Specifically, it will be used to characterize induced pluripotent stem cells (iPSC) and to understand and facilitate the reprogramming process from peripheral blood mononuclear cells (PBMC) to iPSC. Response to therapeutics will be predicted (Aim 1). The Helios CyTOF will be used to help establish peripheral biomarkers from subjects with chronic traumatic encephalopathy or Lewy Body Dementia and correlate to neuropathological and Near Infrared (NIR) spectra based analysis (Aim 2). Single-cell proteomics obtained by Helios CyTOF will be profiled with metabolomics and lipidomics in blood samples from Alzheimer?s disease (AD) patients (Aim 3). Finally, multiple biomarker studies supported by VA and NIH will be corroborated by single-cell proteomic profiling with Helios CyTOF (Aim 4).